Molecular farming is an emerging biotechnology in which plants are used as "biofactories" to produce beneficial bio-products, such as antibodies, enzymes or edible vaccines. Plants provide a safe and low-cost alternative for production of Pharmaceuticals and other therapeutic bio-products. However, the use of transgenic plants as a profitable source of bio-products is limited by low yields caused by a phenomenon known as RNA interference (RNAi) - a sequence-specific RNA degradation pathway that is often triggered by highly expressed transgenes. We propose to implement a promising biotechnology termed amplicon-plus for high-level commercial production of therapeutic bio-products in plants. The patented amplicon-plus technology uses a transgene encoding a replicating RNA viral expression vector (the "amplicon") in conjunction with a naturally occurring suppressor of RNAi as the expression platform for the desired bioproduct. The feasibility of amplicon-plus for commercial production of bio-products will be exemplified using RhinoRx(tm), a recombinant therapeutic protein that is being developed by Planet Biotechnology for prevention of the common cold. The overall plan for the Phase I research is to design and construct amplicon-plus transgenic plants to produce two different forms of RhinoRx(tm), then assay the yield of the products and their biological activity in blocking infection of human cells by the common cold virus. If the amplicon-plus strategy proves effective for high-level production of RhinoRx(tm) in plants, then Phase II research will implement the amplicon-plus technology for the production of the more complex monoclonalantibody- based therapeutic products currently produced by conventional transgenic approaches at Planet Biotechnology. The proposed Phase I research has three specific aims. The first aim is to design and construct amplicon transgenes that are suitable for production of therapeutic proteins in plants. The second aim is to establish anti-RNAi commercial tobacco varieties to improve the yield of the beneficial protein drugs using the amplicon-plus plant system. The final aim is to determine the yield and biological activity of the RhinoRx(tm) produced in the amplicon-plus plants. Development of the amplicon-plus system will enhance the utility of plants as a safe and cost-effective platform for production of therapeutic bio-products.